The gastroduodenal mucus barrier and its role in protection against luminal pepsins: the effect of 16,16 dimethyl prostaglandin E2, carbopol-polyacrylate, sucralfate and bismuth subsalicylate.

Mucus and bicarbonate secretions have been widely implicated as an important pre-epithelial protective barrier against autodigestion of the gastric mucosa by acid and pepsin. Evidence from several independent studies shows there is a continuous layer of resilient viscoelastic mucus gel adherent to the surface of the gastroduodenal mucosa. The median thickness of the adherent gastric mucus layer in humans is 180 microns, range 50-450 microns. The epithelial bicarbonate secretion permeates the unstirred matrix of mucus gel neutralizing luminal acid and establishing a pH gradient within the gel. In the duodenum, evidence supports the mucus bicarbonate barrier as a major protective mechanism against acid aggression. The adherent mucus gel, by acting as an effective 'permeability' barrier to pepsin, protects the underlying sensitive mucosa from digestion. However, pepsin slowly digests mucus gel at its luminal surface to produce soluble degraded mucin. In a rat gastric damage model in vivo, pepsin in excess digests the gastric mucus barrier sufficiently rapidly to outweigh new mucus secretion and lead to breaching of the mucus barrier with the formation of small punctate ulcers in the epithelium accompanied by mucosal haemorrhage. The mucus secretagogue 16,16 dimethyl prostaglandin E2 and the muco-adhesive carbopol-polyacrylate both fully protected the mucosa against pepsin damage by enhancing the protective properties of the mucus barrier. Sucralfate and bismuth subsalicylate were partially effective in protection against pepsin damage but this protection was mainly mediated at the level of the mucosa. In peptic ulcer disease, there is increased mucolytic (mucus degrading) activity in gastric juice and this is associated with an impaired mucin polymeric structure and a weaker mucus barrier.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of mucus in mucosal protection through ethanol and pepsin damage models.

Gastrointestinal mucus is considered an important part of the mucosal defence mechanism against endogenous aggressors such as acid and pepsin. The mucus gel layer, adherent to the mucosal surface creates a diffusion barrier to luminal pepsin, thus protecting the underlying epithelium from the digestion by pepsin. The mucolytic pepsin will, however, digest the mucus at its luminal surface, but that lost is normally balanced by secretion of new mucus. This dynamic balance is disrupted when the mucus is exposed to excess pepsin, which causes focal haemorrhagic damage by progressively hydrolyzing the adherent mucus. The adherent mucus gel layer cannot contribute to the protection against exogen damaging agents such as ethanol and nonsteroidal anti-inflammatory drugs, as these compounds easily penetrate the mucus barrier causing, at high concentration, epithelial exfoliation. This study describes the basic properties and characteristics of gastric mucus and compares the pepsin-induced damage with the ethanol damage model.

GABAA receptors in the rat stomach may mediate mucoprotective effects.

The occurrence and characteristics of binding sites specific for gamma-aminobutyric acid (GABA) and muscimol in the rat stomach were examined by biochemical and autoradiographic techniques, and the effects of GABAergic model compounds on gastric ulceration induced by chemical irritation was studied in intact and unilaterally vagotomized rats. Specific binding sites for [3H]GABA and [3H]muscimol, which showed the characteristics of GABAA receptors, were demonstrated on gastric membranes. Specific muscimol binding sites were found in all regions of the stomach and were present in both the mucosal layer and the remaining tissue of the stomach. Oral pretreatment of the rats with GABA, selective GABAA receptor agonists, or inhibitors of GABA degradation protected the gastric mucosa against the ulcers induced by acidified ethanol (chemical irritant), in both intact and vagotomized rats. These findings are consistent with the view that a subpopulation of GABAA receptors in the rat stomach may mediate the anti-ulcer effect.

Gastrointestinal cytoprotection by indomethacin + sodium salicylate combination in rat.

Non-steroidal antiinflammatory agents are well known to cause gastrointestinal damage in many species including the rat and human. Pelsonin a combination of indomethacin and sodium salicylate (1:10 ratio) has a cytoprotective effect against acidic-alcohol induced gastric necrosis, and it does not induce intestinal ulceration. Pelsonin is capable of blocking the formation of intestinal ulcers induced by oral indomethacin 10 mg/kg (curative cytoprotection). The cytoprotective potency of Pelsonin is due to sodium salicylate.

The evaluation of horizontal resistance of winter wheats by the 'center pivot' method.

Twenty bread wheat varieties were sown in forty meter long plots and infected with a mixture of three races of stem rust (14, 34, 311) in the Center-pivot design. The epidemic's development and its effect on yield (factors) were studied in an experiment.With the Center-pivot method we modelled the natural processes without chemicals. The epidemic's development and the processes connected with it can be studied quantitatively as well as by subjective evaluation.Some of the studied genotypes were quickly infected and others slowly. The date of infection proved to be especially important to the amount of yield decrease.However, a quick spread of the epidemic does not inevitably lead to a decrease of yield and 1000-grain-weight for every genotype.Vertical resistance has qualitative features. On the other hand, there is only a quantitative difference between field resistant and tolerant genotypes, and between horizontally resistant and susceptible ones. The tolerant genotypes cannot limit the spread of the epidemic, but they can limit the degree of damage, and so their yields and 1000-grain-weights are essentially uninfluenced. The field resistant genotypes slow down the epidemic's development, and therefore their yields and 1000-grain-weights decrease less. This fact makes possible their separation in two steps, first on the basis of epidemic development, and then by measuring the decrease of yield and 1000-grainweight.Tolerance and field resistance are supposed to be inherited olygenically. Consequently, breeding for horizontal resistance should work with basically different methods than those previously used for race-specific resistance.